Gender Effects in the Efficacy of Racemic Amphetamine Sulfate in Children with Attention-Deficit/Hyperactivity Disorder

Ann C Childress, Jeffrey H Newcorn, Andrew J Cutler, Ann C Childress, Jeffrey H Newcorn, Andrew J Cutler

Abstract

Introduction: A laboratory classroom study in children aged 6-12 years with attention-deficit/hyperactivity disorder (ADHD) found that racemic amphetamine sulfate (RA-AMPH) significantly improved performance versus placebo from 45 min through 10 h post-dose (NCT01986062). A secondary analysis assessed gender as a potential moderator of response to treatment comparing the ADHD Rating Scale-IV (ADHD-RS-IV) and Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scales.

Methods: After 8 weeks of open-label RA-AMPH dose optimization using improvement in ADHD-RS-IV symptoms as a guide, 97 subjects (38 females and 59 males) were randomized to the sequence of 2 weeks of double-blind treatment with the optimized dose of RA-AMPH followed by placebo or vice versa during a laboratory classroom day. Efficacy measures included the SKAMP and the Permanent Product Measure of Performance (PERMP). The average difference for RA-AMPH versus placebo was estimated using least-square (LS) means. Treatment interaction by gender was analyzed using a cross-sectional fixed-effects model.

Results: ADHD-RS-IV scores were comparable for males and females at study entry and at the end of open-label treatment. During double-blind treatment, LS mean scores significantly improved for both genders versus placebo on the SKAMP scale and the PERMP (average p < 0.0001 for all post-dose time points). Beginning at baseline, males had significantly higher (worse) SKAMP scores than females but not worse ADHD-RS-IV or PERMP scores.

Conclusion: Both genders responded well to treatment with RA-AMPH, with comparable onset and duration of effect. The ADHD-RS-IV and SKAMP scales both measure changes in attention and hyperactive-impulsive behavior, but the SKAMP scale also measures associated disruptive behaviors, such as frustration, lying, and interpersonal conflict, that are more characteristic of oppositional and conduct disorders and more prevalent in boys with ADHD. Therefore, the SKAMP may be more sensitive for measuring the range of symptoms of boys with ADHD than the ADHD-RS-IV.

Funding: Arbor Pharmaceuticals, LLC.

Keywords: Attention-deficit/hyperactivity disorder; Gender; Laboratory classroom study; Racemic amphetamine; Rating scales.

Figures

Fig. 1
Fig. 1
ADHD-RS-IV total scores, ADHD-RS-IV inattention subscale scores, and ADHD-RS-IV hyperactivity/impulsivity subscale scores by gender during the 8-week open-label dose-optimization phase
Fig. 2
Fig. 2
Analysis of laboratory-classroom SKAMP Deportment, SKAMP Attention, and SKAMP Combined scores by treatment and gender. *p < 0.0001 vs. placebo. †p < 0.001 vs. placebo. ‡p < 0.01 vs. placebo. §p < 0.05 vs. placebo
Fig. 3
Fig. 3
Analysis of laboratory-classroom PERMP number of problems attempted and number of problems correct by treatment and gender. *p < 0.0001 vs. placebo. †p < 0.001 vs. placebo. ‡p < 0.01 vs. placebo

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